The protein nutrition of the symbiotic system between /Drosophila/and its gut mic

描述(申请人提供)：肠道微生物区系有助于人类和其他动物的蛋白质营养。这项研究将使用模式昆虫黑腹果蝇来确定宿主如何在生理和遗传上与肠道微生物相互作用，以最大限度地增加蛋白质营养以及整体健康和健身。这一建议的基础是，动物的营养生理和共生是相互依赖的，因此只有当动物蛋白质营养被视为一个共生系统时，才能充分理解它。此外，这种共生系统是高度动态的：对微生物区系或饮食的扰动可以通过宿主营养生理和微生物区系的组成/功能之间的相互作用对蛋白质营养产生重大影响，从而对宿主的健康产生深远影响。果蝇特别容易接受这项研究，因为它在营养需求上与人类高度同源，但它在实验上的优势是拥有一个简单的肠道微生物区系，可以很容易地操纵。果蝇也可以用各种实验性的饮食饲养，从而可以测试饮食组成的影响，模仿人类的饮食行为改变。这项拟议的研究将衡量果蝇饮食和共生操作对蛋白质营养和整体健康和健身的生理影响。它将检验这样一个假设，即宿主在蛋白质前体的同化和分配中的遗传差异是依赖共生关系以实现最大健康的差异的基础，并将使用基因组资源和系统分析来定义支撑共生的表达网络，这些共生对宿主蛋白质营养有不同的影响。这项研究将首次理解肠道共生对宿主蛋白质营养的意义的自然变化背后的机制，这与了解人类的饮食和营养状况及其对健康的影响直接相关。

DESCRIPTION (provided by applicant): The gut microbiota contributes to the protein nutrition of humans and other animals. This study will use the model insect Drosophila melanogaster to determine how hosts interact physiologically and genetically with their gut microbes to maximize protein nutrition as well as overall health and fitness. The basis of this proposal is that the nutritional physiology and symbiosis of animals are interdependent, such that animal protein nutrition can only be understood fully when considered as a symbiotic system. Furthermore, this symbiotic system is highly dynamic: perturbation to the microbiota or diet can have major impact on the protein nutrition, acting through interactions between host nutritional physiology and the composition/function of the microbiota, with profound impacts on the health of the host. Drosophila is particularly amenable to this study because it is highly homologous to humans in its nutritional requirements, but has the experimental advantage of possessing a simple gut microbiota that can be manipulated easily. Drosophila can also be reared on a variety of experimental diets, allowing tests for the effect of diet composition, mimicking dietary behavioral modification in humans. The proposed study will measure the physiological consequences of dietary and symbiotic manipulation on Drosophila on protein nutrition and overall health and fitness. It will test the hypothesis that host genetic variation in the assimilation and allocation of protein precursors underlies variation in dependence on symbiotic associations for maximal health, and will use genomic resources and systems analyses to define the expression networks that underpin symbioses with different impacts on host protein nutrition. This research will achieve the first understanding of the mechanisms underlying natural variation in the significance of the gut symbiosis to host protein nutrition, with direct relevance to understanding human dietary and nutritional conditions and their impacts on health.